RRC ID 21847
Author Ling J, Dubruille R, Emery P.
Title KAYAK-α modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons.
Journal J. Neurosci.
Abstract Circadian rhythms are generated by well-conserved interlocked transcriptional feedback loops in animals. In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on CLK/CYC transcriptional activity, whereas VRI and PDP1 negatively and positively regulate Clk transcription, respectively. Here, we show that the α isoform of the Drosophila FOS homolog KAYAK (KAY) is required for normal circadian behavior. KAY-α downregulation in circadian pacemaker neurons increases period length by 1.5 h. This behavioral phenotype is correlated with decreased expression of several circadian proteins. The strongest effects are on CLK and the neuropeptide PIGMENT DISPERSING FACTOR, which are both under VRI and PDP1 control. Consistently, KAY-α can bind to VRI and inhibit its interaction with the Clk promoter. Interestingly, KAY-α can also repress CLK activity. Hence, in flies with low KAY-α levels, CLK derepression would partially compensate for increased VRI repression, thus attenuating the consequences of KAY-α downregulation on CLK targets. We propose that the double role of KAY-α in the two transcriptional loops controlling Drosophila circadian behavior brings precision and stability to their oscillations.
Volume 32(47)
Pages 16959-70
Published 2012-11-21
DOI 10.1523/JNEUROSCI.1888-12.2012
PII 32/47/16959
PMID 23175847
PMC PMC3528402
MeSH Animals Animals, Genetically Modified / physiology Biological Clocks / genetics Biological Clocks / physiology* Cells, Cultured Circadian Rhythm / physiology* DNA / genetics Drosophila / physiology* Drosophila Proteins / genetics Drosophila Proteins / physiology* Feedback, Physiological / physiology* HEK293 Cells Humans Immunohistochemistry Motor Activity / physiology Neurons / physiology* Neuropeptides / genetics Neuropeptides / physiology Plasmids / genetics RNA, Double-Stranded / biosynthesis RNA, Double-Stranded / genetics Transcription, Genetic / physiology* Transfection
IF 6.074
Times Cited 7
Drosophila 15507R-2 15507R-4 15509R-1 15509R-2